Field of Invention
The disclosed invention relates to electrospray and more specifically to wick based electrospray of analytes. The disclosed invention provides a means for improved electrospray extraction of analytes using a capillarity based fluid delivery system.
Background Description of Prior Art
Electrospray ionization as discovered by Fenn et al in the early 1980's at Yale University essentially launched the field of proteomics, which permitted the detection and study of fragile organic molecules by mass spectrometry. While working Fenn's lab, we used as an electrospray source a needle with a conductive solvent-analyte fluid fed by a hydrostatic source, in this case, a syringe pump. Control of the needle flow rate and applied voltage were important variables to control to produce a good spray and thus transition into a plurality of droplets, which contained the analyte of interest. A counter-current drying gas helped aid the evaporation of the solvent species leaving intact analyte ions in the gas phase with multiple charges. These gas phase ions were then allowed to be introduced into the partial pressure region of the mass spectrometer. During the use of small gauge needles, we found that clogging could be an issue if any particulate contamination were present. In the late 1980's, John Fenn mentioned to the present inventor his having re-read Michael Faraday's “Chemical History of the Candle”. In this treatise, Faraday observed that the capillarity of the wick material regulated the flow of paraffin to the flame. No flame, no capillary flow. The system then, was in perfect balance for fluid flow. In addition, the presence of contaminants that would otherwise cause clogging in a hydrostatically fed electrospray needle would be of no consequence. Accordingly, John tried using various wick materials as electrospray sources, with great success as with many of his innovative and deceptively simple ideas. This work resulted in his “wick” U.S. Pat. No. 6,297,499 issued on Oct. 2, 2001. While the claims in this patent concerned attaching a wick source in direct contact and continuous contact to the analyte-solvent fluid, using the wick to create a self-balancing electrospray introduced into a mass spectrometer, John did offer several other forms of wick sprays not covered by his claims. For example, description is made using any wettable wick structure, whether bundles of small fibers, made of glass, graphite, paper, cotton, and linen have been used with great success. In one adaptation mentioned, flat strips of cloth or paper work just as well as electrospray sources. It was as a result of these wicking properties that the inventor and John Fenn applied the concept to space propulsion (Capillarity Driven Flow of Propellant Liquids in Colloidal Satellite Thrusters), NASA Contract NAS3-02048 in 2001, and Air Force Contract F045-005-0131 in 2005. John offered publicly the use of wicks alone as electrospray sources for many other applications, including air sampling and fluid nebulization. One of the more interesting ideas of John was what is now referred to as “paper spray mass spectrometry”. In such a use, a wettable piece of media, preferably paper, is cut to a sharp point and held in place using a clip such as an alligator clip. Spray fluid, sufficiently conductive to bring about the production of a Taylor Cone and thus an electrospray, is dripped onto the paper. A field is applied between the paper using the aforementioned clip as a pole and with the paper and clip proper combination having a field with respect to a counter pole or electrode. The potential difference between the pole and electrodes is adjusted to allow the formation of the previously described Taylor Cone which results in the production of the now well know electrospray phenomenon. Many investigators have utilized paper spray and similar stand-alone wicking spray mechanisms, but the technology has not been suited toward large-scale drug and proteomic and other use because of several severe limitations. For one, the attachment of the paper or other suitable media to a clip is slow and labor intensive. Care must be taken to preclude contamination between paper samples. Alignment of the paper with respect to axis and distance from the counter electrode is essential. The applied field must be carefully adjusted as does the fluid feed drip rate necessary to wet the paper or other suitable media continuously to provide a steady and/or stable electrospray. Until the present disclosed invention, these limitations have essentially relegated paper spray to the research lab and not the clinical laboratory. The disclosed invention overcomes the need for precise paper alignment, contamination, and offers fully automatic control of fluid and voltage variables all the while permitting use by lay personnel.
In other prior art, Purdue University has been actively investigating paper spray applications after Fenn shared ideas with investigators of that institution over the years from the late 1990's through 2010, and especially during his 90th birthday celebration at Virginia Commonwealth University. In a recent Purdue patent embodiment, a paper source is contained in a polymer cassette. The cassette has a sampling orifice and a contact electrode. In contrast to the disclosed invention, the Purdue device is bulkier, more expensive to produce, and slower to analyze a given sample than the disclosed invention. In addition, the Purdue device cannot provide continuous electrosprays necessary for detailed protein and enzyme studies, being limited to transitory short electrospray bursts. The disclosed invention is not so limited.